1. Field of the Invention
This invention relates to a method of preventing development of multidrug resistance (hereinafter MDR) and to a method of reversing MDR if one already exists thereby to prevent or correct drug accumulation defect in drug resistant cells. More particularly, the invention relates to the administration of masoprocol along with antineoplastic/cytotoxic drugs to which cells develop multidrug resistance (MDR), e.g. Doxorubicin, Daunorubicin, Amsacrine Mitoxantrone, Dactinomycin, Ellipticine, Etoposide, Teniposide, Chlorambucil, Melphalan, Cyclophosphamide, Nitrosoureas BCNU, CCNU, MeCCNU), Methotrexate, Trimetrexate, 5-FU, Ara-C, Ara-A, Cisplatin, Carboplatin and Taxol.
2. Reported Developments
Patients having solid malignant tumors e.g., breast, ovarian, lung, colon and hematological malignant disorders, such as refractory myeloma, often develop MDR . . . . MDR is associated with the overexpression of an MDR-1 gene that codes for a plasma membrane P-glycoprotein. The expression of the MDR-1 gene is believed to be associated with a decreased cellular accumulation of drug due to an active energy dependent efflux mechanism. The active efflux of drug is believed to be mediated by the P-glycoprotein efflux pump.
Attempts have been made to reverse MDR and to correct the drug accumulation defect in drug resistant cells. Among the agents which show promise in vitro are verapamil, quinidine, amioderone, cyclosporin and certain phenothiazines. It appears, however, that in vivo concentrations necessary to reverse MDR cannot be achieved without substantial toxicity to patients.